Identification of useful biomolecular markers in kidney renal clear cell carcinoma: an in silico and in vitro analysis-based study

Background: Kidney renal clear cell carcinoma (KIRC) is the most prevalent type of renal cell carcinoma (RCC), with a high incidence and mortality rate. There is a lack of sensitive biomarkers. Therefore, the discovery of accurate biomarkers for KIRC patients is critical to improve prognosis. Methods: We determined hub genes and their associated pathways involved in the pathogenesis of KIRC from the GSE66272 dataset consisting of KIRC (n = 26) and corresponding control (n = 26) samples and later validated the expression and methylation level of the identified hub genes on The Cancer Genomic Atlas (TCGA) datasets and Human RCC 786-O and normal HK-2 cell lines through RNA sequencing (RNA-seq), Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and targeted bisulfite sequencing (bisulfite-seq) analyses. Results: The identified up-regulated four hub genes include TYROBP (Transmembrane Immune Signaling Adaptor TYROBP), PTPRC (Protein tyrosine phosphatase, receptor type, C), LCP2 (Lymphocyte cytosolic protein 2), and ITGB2 (Integrin Subunit Beta 2). Moreover, the higher expression of TYROBP, PTPRC, LCP2, and ITGB2 in KIRC patients insignificantly correlates with a poor prognosis in KIRC patients. In addition, hub genes were involved in the "Fc epsilon RI signaling pathway, asthma, natural cell killer mediated cytotoxicity, T cell receptor signaling pathway, primary immunodeficiency, Fc gamma R-mediated phagocytosis, malaria, leukocyte transendothelial migration, and legionellosis" pathways and associated with the infiltration level of CD8+ T, CD4+ T, and macrophage cells. Conclusion: Our integrated in silico and in vitro analysis identified important hub genes (TYROBP, PTPRC, LCP2, and ITGB2) involved in the pathogenesis of KIRC as possible diagnostic biomarkers.